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February 17, 2021 - An independent data monitoring committee has concluded that the phase 3 OlympiA trial examining olaparib crossed the superiority boundary for its primary end point of invasive disease-free survival in patients with germline BRCA-mutated, high-risk, HER2-negative early breast cancer.
An independent data monitoring committee has concluded that the phase 3 OlympiA trial (NCT02032823) examining olaparib (Lynparza) crossed the superiority boundary for its primary end point of invasive disease-free survival (iDFS) in patients with germline BRCA-mutated, high-risk, HER2-negative early breast cancer.1
The PARP inhibitor demonstrated a sustainable, clinically relevant treatment effect over placebo when used as an adjuvant treatment in this patient population. No new safety concerns were noted.
The committee has recommended that the trial move to early primary analysis and reporting.
“The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 or BRCA2 genes which also may cause the disease to develop at a significantly earlier age than is usual,” Andrew Tutt, global chair of the OlympiA phase 3 trial and professor of the Institute of Cancer Research and Kings College London, stated in a press release. “The OlympiA trial has allowed us to go beyond using genetic testing to identify patients who are at risk of this disease and explore the potential of [olaparib] to prevent disease recurrence for these patients.”
In the double-blind, parallel group, placebo-controlled, multicenter, phase 3 trial, investigators set out to evaluate the safety and efficacy of olaparib tablets compared with placebo in the adjuvant treatment of patients with BRCA-mutated, high-risk HER2-negative early breast cancer who have finished definitive local treatment and neoadjuvant or adjuvant chemotherapy.
To be eligible for enrollment, patients had to have histologically confirmed nonmetastatic primary invasive adenocarcinoma of the breast that was either triple negative or estrogen receptor and/or progesterone receptor positive, HER2 negative.2
Additionally, patients had to have a germline BRCA1 or BRCA2 mutation predicted to be deleterious or suspected deleterious and an ECOG performance status of 0 or 1. They also needed to have completed acceptable breast and axilla surgery and at least 6 cycles of neoadjuvant or adjuvant chemotherapy that contained anthracyclines, taxanes, or both.
If patients previously received a PARP inhibitor, had a second primary malignancy, were receiving concomitant CYP3A inhibitors, or had evidence of metastatic disease, they were excluded.
In the trial, patients were randomized 1:1 to receive oral olaparib at a twice-daily dose of 300 mg versus placebo. Participants will receive treatment for up to 12 months. Safety assessments are conducted every 2 weeks during the first month, every 4 weeks for the following 5 months and 3 times monthly for the remaining 6 months of study treatment plus 30 days following discontinuation.
After randomization, investigators evaluated participants regularly for signs, symptoms, and evidence of recurrence. Efficacy assessments are conducted 3 times every month during the first 2 years, followed by 6 monthly assessments at year 3, 4, and 5; this will be done on an annual basis thereafter.
The primary end point of the trial was iDFS. Key secondary end points comprised overall survival; distant disease-free survival; effect on the incidence of new primary contralateral breast cancer, new primary ovarian cancer, new primary fallopian tube cancer, and new primary peritoneal cancer; and effect in those identified as having a deleterious or suspected deleterious variant in either of the BRCA genes. Investigators will also perform a pharmacokinetic analysis and evaluate quality of life.
“Analysis of the OlympiA trial, based upon the IDMC recommendation, could represent a potential step forward for patients with early-stage, high-risk primary breast cancer with a germline BRCA mutation,” Roy Baynes, senior vice president and head of Global Clinical Development, as well as chief medical officer of MSD Research Laboratories, added in the release.